Is TBCE p.Val183Phe (c.547G>T) pathogenic?

TBCE p.Val183Phe (c.547G>T) is classified Uncertain significance in TBCE (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-09). AlphaMissense: likely benign (0.1153); Very rare (popmax 0.00535%, afr); Associated with Inborn genetic diseases.

What condition is associated with TBCE p.Val183Phe (c.547G>T)?

TBCE p.Val183Phe (c.547G>T) is associated with Inborn genetic diseases (ClinVar).

How common is TBCE p.Val183Phe (c.547G>T) in the general population?

TBCE p.Val183Phe (c.547G>T) is very rare (popmax 0.00535%, afr) (gnomAD).

What do computational predictors say about TBCE p.Val183Phe (c.547G>T)?

AlphaMissense predicts likely benign (score 0.1153) — an in-silico prediction, not a clinical call.

TBCE p.Val183Phe

c.547G>T · rs754110089 · VCV2399629

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1153 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00535%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1153	likely benign
REVEL	0.042	moderately benign-leaning
SaProt	LLR -4.01	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP -0.48, phastCons 0.34
Regional constraint	o/e 1.00	unconstrained · MANE · 69 kb · p 0.95 · regional, not allelic
Overall
CADD	11.05	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00535% African / African-American · 4/74,836 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000248% 4/1,611,138 alleles · very rare exomes 1/1,458,998 · genomes 3/152,140 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: TBCE
Protein: p.Val183Phe
Coding: c.547G>T
MANE Select: NM_003193
dbSNP: rs754110089
Type: single nucleotide variant
Location: chr1:235427226 (GRCh38)
Gene constraint: LOEUF 0.868 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 89.27 · 6 PDB

Full TBCE gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

B3GALNT2 p.Gly492Ser Uncertain significance ★★ ⚠ same condition
TBCE c.738-3C>T Uncertain significance ★★ same condition
TBCE c.898+5A>G Uncertain significance ★★ same condition
TBCE p.Arg71His Uncertain significance ★★ same condition
TBCE p.Arg88Cys Uncertain significance ★★ ⚠ same condition
TBCE p.Asn87Thr Uncertain significance ★★ ⚠ same condition
TBCE p.Cys141Tyr Uncertain significance ★★ ⚠ same condition
TBCE p.Glu376Asp Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/tbce-p-val183phe (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown